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人类免疫缺陷病毒1型耐药性CCR5-Delta32等位基因在欧洲的空间分布是否是由于历史上罗马扩张导致病原体群落瓦解而形成的?

Is the European spatial distribution of the HIV-1-resistant CCR5-Delta32 allele formed by a breakdown of the pathocenosis due to the historical Roman expansion?

作者信息

Faure Eric, Royer-Carenzi Manuela

机构信息

LATP, CNRS-UMR 6632, Evolution biologique et modélisation, case 5, Université de Provence, Place Victor Hugo, 13331 Marseille Cedex 3, France.

出版信息

Infect Genet Evol. 2008 Dec;8(6):864-74. doi: 10.1016/j.meegid.2008.08.007. Epub 2008 Aug 27.

Abstract

We studied the possible effects of the expansion of ancient Mediterranean civilizations during the five centuries before and after Christ on the European distribution of the mutant allele for the chemokine receptor gene CCR5 which has a 32-bp deletion (CCR5-Delta32). There is a strong evidence for the unitary origin of the CCR5-Delta32 mutation, this it is found principally in Europe and Western Asia, with generally a north-south downhill cline frequency. Homozygous carriers of this mutation show a resistance to HIV-1 infection and a slower progression towards AIDS. However, HIV has clearly emerged too recently to have been the selective force on CCR5. Our analyses showed strong negative correlations in Europe between the allele frequency and two historical parameters, i.e. the first colonization dates by the great ancient Mediterranean civilizations, and the distances from the Northern frontiers of the Roman Empire in its greatest expansion. Moreover, other studies have shown that the deletion frequencies in both German Bronze Age and Swedish Neolithic populations were similar to those found in the corresponding modern populations, and this deletion has been found in ancient DNA of around 7000 years ago, suggesting that in the past, the deletion frequency could have been relatively high in European populations. In addition, in West Nile virus pathogenesis, CCR5 plays an antimicrobial role showing that host genetic factors are highly pathogen-specific. Our results added to all these previous data suggest that the actual European allele frequency distribution might not be due to genes spreading, but to a negative selection resulting in the spread of pathogens principally during Roman expansion. Indeed, as gene flows from colonizers to European native populations were extremely low, the mutational changes might be associated with vulnerability to imported infections. To date, the nature of the parasites remains unknown; however, zoonoses could be incriminated.

摘要

我们研究了公元前和公元后五个世纪古代地中海文明扩张对趋化因子受体基因CCR5(有32个碱基对缺失,即CCR5-Δ32)突变等位基因在欧洲分布的可能影响。有强有力的证据表明CCR5-Δ32突变有单一的起源,它主要在欧洲和西亚被发现,频率总体呈南北递减趋势。这种突变的纯合携带者对HIV-1感染表现出抗性,并且向艾滋病发展的进程较慢。然而,HIV出现的时间显然太晚,不可能成为CCR5的选择压力。我们的分析表明,在欧洲,等位基因频率与两个历史参数之间存在很强的负相关,即古代地中海伟大文明的首次殖民日期,以及罗马帝国最大扩张时期离其北部边境的距离。此外,其他研究表明,德国青铜时代和瑞典新石器时代人群中的缺失频率与相应现代人群中的相似,并且在大约7000年前的古代DNA中发现了这种缺失,这表明过去欧洲人群中的缺失频率可能相对较高。另外,在西尼罗河病毒发病机制中,CCR5发挥抗菌作用,表明宿主遗传因素具有高度的病原体特异性。我们的结果与所有这些先前的数据一起表明,欧洲目前的等位基因频率分布可能不是由于基因传播,而是由于负选择,主要是在罗马扩张期间导致病原体传播。实际上,由于殖民者向欧洲本土人群的基因流动极低,突变变化可能与对输入性感染的易感性有关。迄今为止,寄生虫的性质仍然未知;然而,人畜共患病可能是罪魁祸首。

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